The metabolism, placental transfer, and mechanism of action of various teratogens that affect the craniofacial region and skeletal system are under investigation. Studies with two therapeutically dissimilar drugs, norchlorocyclizine and trifluoperazine, have shown that they induce the same syndrome of malformations of the palate, limbs and vertebral column in rat embryos. Biochemical characterization of the cleft palate defect has shown an acceleration of glycosaminoglycan degradation. Animal models, including rodents and subhuman primates, of specific oral-facial malformations have been developed to evaluate craniofacial development. Teratogens used in these studies include cyclophosphamide and diphenylhydantoin. An in vitro test system using differentiating cells has been developed to assess teratogenic compounds.